In this project a group of basic, clinical and social scientists will investigate aspects of sickle cell disease and provide a service program for individuals with sickle cell conditions. The research projects are designed to answer the following questions. Is the clinical severity of Sickle-B Thalassemia related to the molecular defect? What are the key DNA segments and the trans factors that regulate the expression of globin genes? What is the relationship between the rheological properties of sickle cells and sickle cell membranes to clinical status, hemolysis rate, and cation transport mechanism? What is the immunological basis for age-dependent and type specific variations in antibody response to pneumococcal polysaccharide antigens? What are the factors that govern the rate of sickling and desickling? What is the nature and mechanism of abnormalities of cell mediated immune function in zinc deficient sickle cell anemia patients? What is the effect of zinc supplementation on growth and development of zinc deficient individuals who have sickle cell anemia? What are the social factors and coping processes related to adjustment of school-aged children with sickle cell anemia? The service programs are designed: to inform the Black population about sickle cell conditions and to motivate those in the child bearing age to seek testing; counsel those who are identified as having sickle cell trait so that they can make informed self interest decisions; to permit mothers who are pregnant with a child with sickle cell anemia to make informed self interest decisions with respect to continuing or terminating the pregnancy; and to prevent premature death in young children with sickle cell anemia from pneumococcal sepsis and acute splenic sequestration.